Hyperglycaemia attenuates erythromycin-induced acceleration of solid-phase gastric emptying in idiopathic and diabetic gastroparesis.

BACKGROUND: Erythromycin has recently been found to be a gastrointestinal prokinetic agent in humans. Acute hyperglycaemia has been associated with delayed gastric emptying in both healthy controls and diabetic patients. Our aim was to investigate in gastroparetic patients (diabetics and idiopathics) whether hyperglycaemia, per se, reduces gastric motility during erythromycin-induced acceleration of gastric emptying of solids. METHODS: In 12 gastroparetic patients, 6 diabetics and 6 idiopathics, gastric emptying of solids was measured scintigraphically after giving placebo in normoglycaemia (5-8.9 mmol/l glucose) or 200 mg erythromycin lactobionate intravenously in normo- or hyperglycaemia (16-19 mmol/l glucose) induced by intravenous glucose infusion in random order on separate days. RESULTS: Erythromycin in normoglycaemia accelerated solids gastric emptying compared with placebo in all patients by abolishing the lag-phase duration and by decreasing the retained percentage of a meal in the stomach at 120 and 150 min (14.5% +/- 5.3% versus 88.4% +/- 10.6% and 3.5% +/- 2.1% versus 70.1% +/- 15.4%, respectively) (P < 0.001). The retained isotopic percentage in the stomach after erythromycin in induced hyperglycaemia compared with erythromycin in normoglycaemia, at 120 and 150 min, was increased (51.9% +/- 9.8% versus 14.5% +/- 5.3%, and 24.5% +/- 5.9% versus 3.5% +/- 2.1%, respectively) (P < 0.001) but was decreased in comparison with placebo (P < 0.001). A significantly increased percentage of isotope was retained in the stomach of the diabetic patients at 120 and 150 min, compared with the idiopathics, only after giving erythromycin in the hyperglycaemic condition (57.6% +/- 8.7% versus 46.1% +/- 7.6% (P = 0.036) and 27.8% +/- 5.7% versus 21.1 +/- 4.4% (P = 0.040), respectively). CONCLUSIONS: Hyperglycaemia attenuates erythromycin-induced acceleration of solid-phase gastric emptying in idiopathic and diabetic gastroparesis and increases the retained isotopic meal in the stomach. Hyperglycaemia reduces gastric motility more in the diabetic patients with gastroparesis than in idiopathic patients.     

糖尿病病人胃排空功能的研究

用Ｂ超观察了２２例糖尿病病人折胃排空功能变化。１３例有胃排空延缓，占全组５９．９９％，主要表现为胃全排空时间的延长。胃排空延缓与病程及慢性病变相关，且糖尿病胃排空延缓组较排空非延缓组餐后血糖值明显增高，故糖尿病胃排空延缓既可能是糖尿病的又一慢性病变，也可能受到高血糖本身的调控。     

Progression of changes in gastric emptying of hypertonic liquids after proximal gastric vagotomy

Gastric emptying rates of hypertonic (10%) dextrose liquid meals were studied in five dogs before, and 3, 6, and 12 months after proximal gastric vagotomy (PGV) without drainage. The purpose of this study was to determine if operation-related changes in emptying rates normalized or became more disparate during the year after PGV. An increased rate of emptying during the first 5 min after ingestion was seen at 3 months after PGV, which significantly increased (P<0.025) after 6 and 12 months. The remainder of the meal after PGV emptied at a regulated exponential rate unchanged throughout the postoperative year from its preoperative rate. Total volumes of gastric aspirate at four intervals after meal ingestion did not significantly change across the four test periods in respect to endogenous secretion or pH acidity.Supported by The Veterans Administration.     

Effect of metoclopramide on gastric liquid emptying in patients with diabetic gastroparesis

Metoclopramide tablets have been approved for use in the acute and chronic management of diabetic gastroparesis. Its efficacy as an antiemetic has been well documented. We measured the acute and chronic effects of oral metoclopramide on gastric liquid emptying in 12 diabetic patients with symptoms of stasis using scintiscanning techniques. We found that liquid emptying in these subjects was abnormal, as determined by residue area determination when compared to normal volunteers (P<0.01). Metoclopramide 10 mg orally acutely enhanced emptying, restoring it to control values (P<0.01). In contrast, when gastric emptying was evaluated following one month of chronic liquid metoclopramide use, 10 mg before each meal, the acute effect of the drug on emptying could no longer be demonstrated and residue areas returned to baseline values, suggesting that chronic oral administration of metoclopramide may result in a loss of the gastrokinetic properties of this drug.This work was supported in part by the Wechsler Research Foundation, No. 538475 and the Hunt Foundation. Dr. Van Thiel is the recipient of a Career Development Award from the National Institutes of Mental Health, No. AA00016.     

Effect of motilin on gastric emptying in patients with diabetic gastroparesis.

Erythromycin markedly accelerates gastric emptying, possibly because it acts as a motilin agonist. In the present study, the effect of an equipotent dose of motilin was tested. In six patients with severe diabetic gastroparesis, gastric emptying of liquids and solids was examined scintigraphically after motilin or placebo in a double-blind crossover study. Motilin (10 pmol.kg-1.min-1) or saline was infused over a 90-minute period starting 5 minutes before breakfast. Motilin markedly accelerated emptying. For liquids, the half-emptying time was reduced from 51 +/- 6 to 22 +/- 11 minutes (P less than 0.01) and for solids from 111 +/- 4 to 51 +/- 12 minutes (P less than 0.01). The mean increase in plasma motilin levels was 1315 +/- 342 pg/mL, corresponding to an effective infusion rate of about 4 pmol.kg-1.min-1. In the control experiments, basal motilin levels (173 +/- 17 pg/mL) were within the normal range but increased steadily postprandially, reaching 321 +/- 25 pg/mL at the end of the study period, probably reflecting gastric distension. The postprandial increase in pancreatic polypeptide level was blunted compared with accepted normal values but was more pronounced during motilin infusion, i.e., 650 +/- 217 vs. 279 +/- 66 pg/mL (P less than 0.01), probably because of the improved emptying. Our data show that motilin accelerates gastric emptying in diabetic gastroparesis and support the hypothesis that erythromycin's effect is mediated through motilin receptors.     

Comparison between gastric emptying of digestible and indigestible solids in diabetic patients

Summary We measured simultaneously gastric emptying of digestible and indigestible solids in 10 normal subjects and in 14 insulin-requiring diabetic patients. Our results demonstrate that in both diabetics and in controls the gastric emptying of digestible and indigestible solids occurs during the same phase of gastric motor activity, i.e. during the post-prandial period. However, gastric emptying of both digestible and indigestible solids is delayed in diabetic patients compared to controls.     

高龄糖尿病患者血糖与胃排空的相互关系

目的研究高龄糖尿病(DM)患者胃排空与血糖间的关系。方法将63例2型糖尿病(T2DM)患者根据血糖控制情况分成2组(血糖控制正常组DM1和血糖异常组DM2),均给予99mTc标记的试餐,测定固相胃排空时间,并与30例正常对照组比较,对DM2组中胃排空延迟者给予莫沙比利5 mg,3次/d,服药4 w后再测放射性核素胃排空及血糖。结果DM2组胃半排空时间延迟,平均(106.9±29.5)m in,与正常对照组(78.1±19.6)相比,P<0.05,DM1组胃半排空时间(76.5±17.1)m in,与正常对照组相比,P>0.05。DM2组中17例血糖异常胃排空延迟者服用莫沙比利后,胃半排空时间明显改善,平均为(81.3±15.2)m in;服药后空腹血糖无变化,8例餐后血糖降低,4例上升,平均餐后血糖与服药前相比,变化无显著差异。结论高龄DM患者高血糖时可延迟胃排空;改善胃排空后可降低部分病人的餐后血糖,空腹血糖无变化。     

Gastric myoelectrical activity and gastric emptying in diabetic patients with dyspeptic symptoms

INTRODUCTION Recently, electrogastrography(EGG) has received more andmore attention.     

Prevalence and determinants of delayed gastric emptying in hospitalised Type 2 diabetic patients

AIM： To determine the prevalence of delayed gastric emptying （GE） in older patients with Type 2 diabetes mellitus. METHODS： One hundred and forty seven patients with Type 2 diabetes, of whom 140 had been hospitalised, mean age 62.3 ± 8.0 years, HbA1c 9.1% ± 1.9%, treated with either oral hypoglycemic drugs or insulin were studied. GE of a solid meal （scintigraphy）, autonomic nerve function, upper gastrointestinal symptoms, acute and chronic glycemic control were evaluated. Gastric emptying results were compared to a control range of hospitalised patients who did not have diabetes. RESULTS： Gastric emptying was delayed （T50 〉 85 min） in 17.7% patients. Mean gastric emptying was slower in females （T50 72.1 ± 72.1 min vs 56.9 ± 68.1 min, P = 0.02） and in those reporting nausea （112.3 ± 67.3 vs 62.7 ± 70.0 min, P 〈 0.01） and early satiety （114.0 ± 135.2 vs 61.1 ± 62.6 min, P = 0.02）. There was no correlation between GE with age, body weight, duration of diabetes, neuropathy, current glycemia or the total score for upper gastrointestinal symptoms. CONCLUSION： Prolonged GE occurs in about 20% of hospitalised elderly patients with Type 2 diabetes when compared to hospitalised patients who do not have diabetes. Female gender, nausea and early satiety areassociated with higher probability of delayed GE.     

Pancreatic polypeptide secretion in diabetic patients with delayed gastric emptying and autonomic neuropathy

Measuring postprandial pancreatic polypeptide (PP) plasma concentration is a sensitive method for autonomic nervous system assessment. Delayed gastric emptying (DGE) often does not correlate clearly with cardiac autonomic neuropathy (CAN). This study was conducted to evaluate whether decreased PP secretion (PPS) accompanies DGE and CAN in diabetes. Fourteen long-standing diabetics with DGE assessed by scintigraphy (group A), 14 well-matched diabetics with normal gastric emptying (NGE) (group B), and 12 healthy controls (group C) were the study subjects. CAN and postprandial PPS at 0, 30, and 60 min after test meal ingestion were examined in all the subjects, and the area under curve of PP secretion was calculated. There was no correlation between DGE and CAN (eight diabetics with CAN in A and six in B). Basal PP values were almost the same in all the patients (mean 77.27 ± 11.0 pg/mL). The area under curve of PP secretion values (PP_AUC) after test meal ingestion were significantly higher in B (211.84 ± 36.13 pg/mL/h; p < 0.0001) and C (233.68 ± 23.43 pg/mL/h; p < 0.00001) than in A (147.59 ± 31.77 pg/mL/h). Diabetics with CAN had lower PPS expressed as PP_AUC than those without CAN, which was independent of gastric emptying rate (152.31 ± 37.18 versus 207.12 ± 39.21 pg/mL/h; p < 0.001). There were no significant differences between test meal-stimulated PP_AUC in diabetics without CAN (207.12 ± 39.21 pg/mL/h) and controls (233.68 ± 23.43 pg/mL/h), and this was also independent of gastric emptying rate. In patients with both DGE and CAN, the PPS was completely blunt (PP_AUC 124.04 ± 5.71 versus 233.68 ± 23.43 pg/mL/h in controls; p < 0.001). The PPS in diabetics with CAN and NGE was significantly lower than in controls (PP_AUC 190.0 ± 37.45 versus 233.68 ± 23.43 pg/mL/h; p < 0.01). In conclusion, the PPS in diabetics with CAN was decreased significantly and independently of DGE. The PP secretion was very low in diabetics with both CAN and DGE.     

三维超声检测糖尿病胃轻瘫患者胃排空功能的研究

目的应用三维超声扫描技术检测2型糖尿病患者胃液体半排空功能的改变,以利于糖尿病性胃轻瘫的诊断和治疗。方法采用三维超声技术检测30例2型糖尿病患者及20例健康志愿者进食液体试餐后胃排空的指标,经计算机拟合出不同时点胃容积的变化,计算出胃半排空时间（T1/2）、胃排空时间（T）及液体胃排空曲线,并与正常对照组比较。结果2型糖尿病胃轻瘫组胃半排空时间及胃排空时间均较正常对照组延长,30名糖尿病患者中有17名患者存在胃排空延迟,约占56．7％。结论应用三维超声技术检测液体胃排空功能,方法简单易行、患者易接受、可多次重复。为临床诊断糖尿病性胃轻瘫提供一种可靠、无创性的检测手段。     

Relationship between acceleration of gastric emptying and oesophageal acid exposure in patients with endoscopy-negative gastro-oesophageal reflux disease

OBJECTIVE: A delay in gastric emptying has been reported in patients with gastro-oesophageal reflux disease (GORD), but its role in increasing the number of reflux episodes is still debated. The aim of this study was to assess the relationship between acceleration of gastric emptying and gastro-oesophageal reflux in patients with endoscopy-negative GORD and pathological oesophageal acid exposure. MATERIAL AND METHODS: Twelve patients (7 M, age range 24-65 years) underwent 6-h postprandial (2.1 MJ meal) combined gastric emptying by real-time ultrasonography and intra-oesophageal pH monitoring after cisapride (20 mg b.i.d.) and placebo for 3 days, on two separate occasions at least 7 days apart in double-blind randomized order. Gastric emptying after placebo was also measured in 12 healthy volunteers (7 M, age range 25-54 years). RESULTS: In the patients' group, the area under the emptying time curve was greater (p<0.01), and half and total emptying times prolonged (p<0.01) compared to the healthy subjects, 115 min (mean)+/-6 (SEM) versus 86+/-6 and 232 min+/-16 versus 160+/-7, respectively. Cisapride accelerated both half- and total gastric emptying (p<0.02): -22 min (mean); -10 to -34 (95% CI) and -48 min; -10 to -85, respectively, decreased both percentage of time at pH < 4 (p<0.01) and number of reflux episodes (p<0.05). However, no relationship was found between changes in gastric emptying and in the reflux variables by linear regression analysis (R2<0.005). CONCLUSION: The emptying rate of the whole stomach is not a major determinant of gastro-oesophageal reflux.     

Relationship between acceleration of gastric emptying and oesophageal acid exposure in patients with endoscopy-negative gastro-oesophageal reflux disease

Objective. A delay in gastric emptying has been reported in patients with gastro-oesophageal reflux disease (GORD), but its role in increasing the number of reflux episodes is still debated. The aim of this study was to assess the relationship between acceleration of gastric emptying and gastro-oesophageal reflux in patients with endoscopy-negative GORD and pathological oesophageal acid exposure. Material and methods. Twelve patients (7 M, age range 24–65 years) underwent 6-h postprandial (2.1 MJ meal) combined gastric emptying by real-time ultrasonography and intra-oesophageal pH monitoring after cisapride (20 mg b.i.d.) and placebo for 3 days, on two separate occasions at least 7 days apart in double-blind randomized order. Gastric emptying after placebo was also measured in 12 healthy volunteers (7 M, age range 25–54 years). Results. In the patients’ group, the area under the emptying time curve was greater (p<0.01), and half and total emptying times prolonged (p<0.01) compared to the healthy subjects, 115 min (mean)±6 (SEM) versus 86±6 and 232 min±16 versus 160±7, respectively. Cisapride accelerated both half- and total gastric emptying (p<0.02): ?22 min (mean); ?10 to ?34 (95% CI) and ?48 min; ?10 to ?85, respectively, decreased both percentage of time at pH?p<0.01) and number of reflux episodes (p<0.05). However, no relationship was found between changes in gastric emptying and in the reflux variables by linear regression analysis (R²<0.005). Conclusion. The emptying rate of the whole stomach is not a major determinant of gastro-oesophageal reflux.     

Measurement by epigastric impedance of gastric emptying in diabetic autonomic neuropathy

Changes in impedance across the epigastrium form the basis of a new non-invasive method of assessing gastric emptying of liquids. The apparatus is simple to use at the bedside and, in conjunction with conventional investigations, is of value in diagnosing gastroparesis in patients with diabetic autonomic neuropathy and symptoms of recurrent vomiting. We measured gastric emptying of liquids in 22 diabetics aged 33.4 +/- 9 years (mean +/- SD) with severe symptomatic autonomic neuropathy (mean heart rate variability 4.9 +/- 2.2 SD beats/min), and 15 normal controls. Median 'half emptying' time in the diabetics with autonomic neuropathy was prolonged overall but it was not always abnormal (12.25 min, range 6.5-greater than 30 compared to 8.0 min, range 3-17; p less than 0.01). Results in five diabetics with symptoms of recurrent vomiting corresponded with those using conventional radiological methods, confirming gastroparesis in three instances and excluding it in two. The effect of metoclopramide was also studied and was shown to accelerate gastric emptying in some but not all of the patients. Assessment of gastric emptying using the impedance method assists in establishing the diagnosis of gastroparesis and is of value for repeated measurements.     

Rapid gastric emptying in duodenal ulcer patients

Isosmotic liquid peptone meals adjusted to pH 7, 3, and 1.5 were instilled on separate days into the stomachs of 8 duodenal ulcer patients and 7 healthy controls. Using a marker-dilution method, duodenal acid load (DAL) was measured as the amount of unbuffered hydrogen ions delivered to the duodenum per unit time. Gastric emptying was measured as the total volume of gastric contents, including meal plus gastric secretion, passing through the pylorus per unit time (VPP). Mean pentagastrin-stimulated acid output was not significantly different between the two groups. However, after all three test meals, mean DAL was significantly greater in duodenal ulcer than in normal subjects in both hours of the test, and VPP was significantly greater in ulcer than in normal subjects in the first 40 min. In both groups, following peptone meals of pH 7 and 3, the volume of gastric contents delivered through the pylorus decreased as the amount of free hydrogen ions entering the duodenum increased, but a given load of acid was less effective in slowing emptying in duodenal ulcer patients than in controls. These studies indicate that duodenal ulcer patients empty liquid meals more rapidly than do normal subjects, independent of the initial pH of the meals, and that, in addition, acid inhibition of gastric emptying is defective in duodenal ulcer.Dr. Grossman died May 26, 1981.S. K. Lam was a visiting scientist from the Department of Medicine, University of Hong Kong. Queen Mary Hospital, Hong Kong. M.I. Grossman holds a Veterans Administration Senior Medical Investigatorship.These studies were supported by National Institutes of Arthritis, Metabolism and Digestive Diseases grant AM 17328 to the Center for Ulcer Research and Education and by Veterans Administration Research Funds.This work was presented in part in abstract form at the 80th Annual Meeting of the American Gastroenterological Association, New Orleans, Louisiana, May 19–25, 1979.     

Metoclopramide therapy in patients with delayed gastric emptying

Twenty-eight patients with delayed gastric emptying as measured by an abnormal barium burger were treated with metoclopramide in a randomized, double-blind fashion. Five had diabetic gastroparesis, four had undergone vagotomy and pyloroplasty, and 19 were idiopathic. Patients received either metoclopramide or placebo for a three-week period and symptoms were scored prestudy, at weekly intervals, and at termination of the study. Ten of 14 patients on metoclopramide and four of 14 on placebo decreased their symptom score to a level below entry criteria, indicating a significant metoclopramide effect when compared to placebo. The mean total symptom score for the metoclopramide group was 18.4 prestudy and 7.2 poststudy while for placebo was 19.1 prestudy and 12.9 poststudy. Although improvement on placebo was significant, these patients were still symptomatic. The improvement on metoclopramide was significantly greater than the improvement on placebo. Metoclopramide is an effective agent in treating the symptom complex of delayed gastric emptying.     

Delayed gastric emptying in patients with liver cirrhosis

Using a scintigraphic technique, we investigated gastric emptying of a semisolid meal in 20 patients with liver cirrhosis and in 10 control subjects and correlated gastric emptying with gastrointestinal symptoms and with autonomic nervous function as determined by R-R interval variation on the electrocardiogram. All subjects lacked endoscopic abnormalities that might explain their gastrointestinal symptoms. None had alcoholic liver disease, diabetes, or other diseases known to affect gastric emptying. The half-time for gastric emptying was significantly prolonged in the cirrhotic patients (51.3±16.6 minutes) as compared with control subjects (29.9±8.4) (P<0.01). There was a significant correlation between the gastrointestinal symptom score and the half-time for gastric emptying (r=0.46,P<0.05) in the cirrhotic patients. However, the decreases in R-R interval variation and gastric emptying were not significantly correlated. These observations indicate that delayed gastric emptying is frequently present in patients with liver cirrhosis and may produce their gastrointestinal symptoms.